The Role of the Adrenergic System in Neurodegeneration and Oxidative Stress-Induced Damage to the Brain

Abstract

Stress is one of the major contributing factors to the development of neurodegenerative diseases and mental disorders. These pathologies are reportedly characterized by progressive loss of neurons and impaired motor and cognitive functions. Changes in stress-induced mechanisms, such as oxidative stress (OS) with corresponding neurotransmitters’ interplay are important for both, the mechanisms of defense and the progression of mental disorders. OS implies an imbalance in the pro-oxidant/antioxidant homeostasis resulting in the generation of aggressive radicals, reactive oxygen species (ROS), and exaggeration of neurodegenerative disease. However, in clinical trials, antioxidants such as alfa-tocopherol have not provided efficacious protection as an alternative therapy for neurodegenerative diseases. Norepinephrine (NE) is the main stress hormone capable of modulating the stress response and providing neuroprotection during neurodegeneration by limiting the production of ROS and stimulating the antioxidative defense, especially against the OH^• radical. This in turn leads to the protection of cells from ROS-mediated damage and the improvement of cognitive and behavioral functions. Mounting evidence from preclinical studies in the last decade suggests the α2-adrenoblockers-mediated increase of NE release in the brain to be a promising therapeutic approach in neurodegenerative diseases. In this review, we focus on the role of (1) OS in neurodegenerative diseases; (2) the role of adrenergic receptors (ARs) in disease pathology and mechanisms of defense during neurodegeneration, and (3) the adrenergic signaling system in cognitive functions and neuroprotection provided by NE and α2-adrenoblockers.